Smoldering Multiple Myeloma: Dousing the Fire?

Michael E. Williams, MD

Lenalidomide plus dexamethasone delayed progression and improved survival in patients with high-risk SMM.

Observation without treatment until disease progression has been the standard of care for patients with smoldering multiple myeloma (SMM). To test the ability of lenalidomide plus dexamethasone therapy to delay the time to progression (TTP) to symptomatic myeloma, investigators conducted a randomized, open-label, phase III trial involving patients with high-risk SMM (defined as ≥10% marrow plasma cells, immunoglobulin G paraprotein ≥3 gm/dL or immunoglobulin A ≥2 gm/dL, or urinary paraprotein >1 gm/24 hours).

A total of 119 patients were randomized to observation or induction treatment with lenalidomide (25 mg/day for 21 days) and dexamethasone (20 mg on days 1–4 and 12–15) in 28-day cycles, followed after 9 cycles by maintenance therapy with lenalidomide (10 mg/day) for 21 days of each 28-day cycle, for a total of 2 years of therapy.

The overall response rate was 79% after induction therapy, increasing to 90% with maintenance therapy; the complete response rate increased from 21% to 38%. After a median follow-up of 40 months, the median TTP (the primary endpoint) was significantly improved with treatment versus observation (not reached vs. 21 months; P<0.001), as was the 3-year overall survival rate (94% vs. 80%; P=0.03). Four deaths occurred in the treatment arm (2 from disease progression) versus 13 deaths in the observation arm (all from disease progression).

Citation(s):

Mateos M-V et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 2013 Aug 1; 369:438.